CN104045583B - A kind of method preparing substituted-amino carbamide compound - Google Patents

A kind of method preparing substituted-amino carbamide compound Download PDF

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CN104045583B
CN104045583B CN201410257409.1A CN201410257409A CN104045583B CN 104045583 B CN104045583 B CN 104045583B CN 201410257409 A CN201410257409 A CN 201410257409A CN 104045583 B CN104045583 B CN 104045583B
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urea
amino
substituted
nitrogen benzide
iodide
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CN104045583A (en
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毛金成
刘德福
荣光伟
晏宏
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Suzhou University
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Suzhou University
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Abstract

The invention discloses a kind of preparation method of substituted-amino carbamide compound; concrete steps are: under air conditions, with azobenzene compound and amides for reactant, with iodide; acyl chlorides and oxygenant are catalyst system, prepare substituted-amino carbamide compound by hydroacylation reaction.In this method, raw material is stablized, and cheap and easy to get, and solvent load is very little, without the need to the solvent of a large amount of strong acid and strong bases; Three-waste free discharge, meets the requirement of Green Chemistry.

Description

A kind of method preparing substituted-amino carbamide compound
Technical field
The invention belongs to the preparing technical field of Ammonia organic compound, be specifically related to a kind of preparation method of substituted-amino carbamide compound.
Background technology
Substituted-amino urea is the extremely useful important fine chemicals of a class and industrial chemicals, due to the peptide bond (-CO-NH-) containing different replacement in structure, therefore mostly there is biological activity, can extensively be used as weedicide, sterilant, plant-growth regulator and pharmaceutical intermediate, and the structural unit of the biologically active substance such as many picture enzyme inhibitorss, biosimulation peptide also containing asymmetry substitute urea.
Conventional synthesis Urea,amino-compounds, main method utilizes the addition reaction of isocyanic ester and amine (see ArrietaA, PalomoC, TetrahedronLett.1981,22:1729-1732), because isocyanic ester is unstable, be not easy to store, and the phosgene of the preparation severe toxicity of isocyanic ester, production is absolutely unsafe.N-substituted trichloroacetamide is one of substitute of hypertoxic phosgene, be easy to be reacted under phosphorus trichloride exists by amine and trichoroacetic acid(TCA) prepare, it is the corresponding isocyanic ester of in-situ preparation under the effect of mineral alkali, do not need to be separated directly and amine or acid amides react, for substitute urea compound provide one more clean, convenient and efficiently synthetic method (see Chin.J.Synth.Chem.1995,3,253), but temperature of reaction requires strict, the easy generation tree resinous material of reaction process, thus reduce reaction yield.
Chen Tianyun for raw material, uses water as solvent with phenylhydrazine hydrochloride and urea, synthesize under sulphuric acid catalysis 1-Carbaphen (see the study on the synthesis of Su Xin Chen Tian cloud Wang Hua .1-Carbaphen. chemistry world 2010.7.429).But the solvent load of aforesaid method is excessive, easily produce a large amount of waste water; And there is potential safety hazard in the vitriol oil.
Therefore find raw material sources extensive, reaction process is simple, product yield is high, safety, environmental protection, low cost preparation method be necessary effectively to synthesize substituted-amino carbamide compound.
Summary of the invention
The object of this invention is to provide that a kind of reaction process is simple, product yield is high, safety, environmental protection the method preparing substituted-amino carbamide compound.
To achieve the above object of the invention, the technical solution used in the present invention is:
A kind of method preparing substituted-amino carbamide compound, comprise the following steps: with azobenzene compound and Carbox amide for reactant, with iodide, acyl chlorides and oxygenant for catalyst system, prepare product substituted-amino carbamide compound through hydroacylation reaction;
Wherein, described azobenzene compound is nitrogen benzide, 4,4 '-dimethyl nitrogen benzide, 4,4 '-dimethoxy nitrogen benzide, 4,4 '-dichloro nitrogen benzide, 4,4 '-dibromo nitrogen benzide, 4,4 '-two trifluoromethoxy nitrogen benzide, 3,3 '-dichloro nitrogen benzide, 3,3 '-dichloro nitrogen benzide, 2, the one in 2 '-dichloro nitrogen benzide, 4-iodine nitrogen benzide, 4-chlorine nitrogen benzide, 4-bromine nitrogen benzide, 1-(4-bromophenyl)-2-(4-iodophenyl) diazene;
Described Carbox amide is DMF, N, N-diethylformamide, N, N-dibutyl formamide, N-N-formyl morpholine N-, methane amide or N-METHYLFORMAMIDE;
Described iodide are selected from potassiumiodide, elemental iodine, sodium iodide, tetrabutylammonium iodide, ammonium iodide wherein one or more mixture;
Described oxygenant is tertbutyl peroxide, di-t-butyl peroxide or dicumyl peroxide;
Described acyl chlorides is Benzoyl chloride, phenyllacetyl chloride, Bian chlorine, nitrogen nitrogen dimethyl methyl acyl chlorides, Acetyl Chloride 98Min., chloroacetyl chloride a kind of or its more than one mixture;
In described catalyst system, the mass ratio of iodide and oxygenant is 1: 10 ~ 40;
The general structure of described substituted-amino carbamide compound is:
or
Wherein, R 1, R 2, R 3, R 4be selected from the one in following scheme:
(1) R 3, R 4for methyl, R 1, R 2independently be selected from the one in hydrogen, methyl, ethyl, methoxyl group, oxyethyl group, trifluoromethoxy, chlorine, bromine, iodine;
(2) R 1, R 2for hydrogen, R 3, R 4independently be selected from hydrogen, methyl, ethyl;
R 5, R 6independently be selected from the one in hydrogen, methyl, ethyl, methoxyl group, oxyethyl group, trifluoromethoxy, chlorine, bromine, iodine.
In technique scheme, the concrete steps preparing substituted-amino carbamide compound, for iodide, oxygenant, acyl chlorides and reactant are placed in reactor, at 80 ~ 140 DEG C, are reacted and are prepared product in 12 ~ 36 hours.
In technique scheme, in described catalyst system, the mass percent of iodide is 2% ~ 8%.
In technique scheme, the mol ratio of described azobenzene compound and iodide is 1: 0.1 ~ 0.2; The mol ratio of azobenzene compound and oxygenant is 1: 2 ~ 4.The consumption of oxygenant crosses that I haven't seen you for ages makes reaction efficiently carry out, but the consumption of oxygenant is crossed conference and increased reaction cost and the aftertreatment affecting reaction system.
In technique scheme, the mol ratio of described azobenzene compound and Carbox amide is 1: 45 ~ 55; Carbox amide, both as substrate, is also used as solvent.
In preferred technical scheme, temperature of reaction is 120 DEG C; Reaction times is 24 hours.
In preferred technical scheme, purify after reaction terminates, be specially and first distill, then by concentrated solution by simple column chromatography, substituted-amino carbamide compound can be obtained.
In technique scheme, described distillation, to obtain the operations such as substituted-amino urea finally by rapid column chromatography and all belong to prior art, wherein used extraction agent, siccative, eluent are also prior aries, those skilled in the art can select suitable reagent according to the character of final product, and in preferred technical scheme, eluent is ethyl acetate/petroleum ether system (volume ratio is 1: 3).
The present invention's reaction is carried out in atmosphere, can not have a negative impact to reaction.
Technique scheme can be expressed as follows:
Because technique scheme is used, the present invention compared with prior art has following advantages:
1. the present invention first in atmosphere, with azobenzene compound and Carbox amide for reactant, formed catalyst system, prepare substituted-amino carbamide compound by shortening acylation reaction with iodide, oxygenant and acyl chlorides; The catalyst levels used is little, and cheap and easy to get; Without the need to plus solvent, avoid the use of strong acid and strong base solvent in prior art.
2. method disclosed by the invention compared with prior art, and raw material is stablized, and reaction shortens to single step reaction; Aftertreatment is simple, is conducive to the purifying of product; The prior use being that of avoiding hypertoxic phosgene, unsafe vitriol oil.
3. the raw material sources of the present invention's use are extensive, cheap and easy to get; Reaction process is simply controlled, and reaction conditions is gentle, and only need air, reaction cost is low; Three-waste free discharge, meets Green Chemistry requirement; Product yield is high; Be suitable for suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the invention will be further described
Embodiment one
Nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N is loaded successively in a Schlenk test tube, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-dimethyl-1,2-diphenyl amino urea, yield is 65%.Its nuclear magnetic data is: 1hNMR (400MHz, DMSO) δ 8.45 (s, 1H), 7.29 (t, j=7.9Hz, 2H), 7.16 (t, j=7.9Hz, 2H), 7.12 – 7.06 (m, 2H), 7.03 (t, j=7.3Hz, 2H), 6.81 (d, j=7.6Hz, 2H), 6.73 (t, j=7.3Hz, 1H), 2.84 (s, 6H). 13cNMR (101MHz, DMSO) δ 164.69,153.46,150.22,134.17,133.89,128.37,125.33,123.98,117.09,42.49. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 18n 3orequires256.1450, found256.1448.
Embodiment two
Nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N is loaded successively in a Schlenk test tube, dinethylformamide (2ml), di-t-butyl peroxide (1mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-dimethyl-1,2-di-p-tolyl Urea,amino-, yield is 20%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.42 (d, j=7.4Hz, 2H), 7.36 (d, j=7.7Hz, 2H), 7.12 (m, 2H), 7.00 (t, j=8.1Hz, 1H), 6.89 (d, j=7.8Hz, 1H), 6.81 (s, 1H), 2.96 (d, 6H), 2.33 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 156.31,148.02,133.24,131.61,131.28,129.55,129.48,124.96,113.14,39.62,21.42. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 17h 22n 3orequires284.1763, found284.1760.
Embodiment three
Nitrogen benzide (0.5mmol), sodium iodide (0.05mmol) and N is loaded successively in a Schlenk test tube, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, 2-bis-(4-p-methoxy-phenyl)-N, N-dimethylamino urea, yield is 30%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.26 (d, j=9.0Hz, 2H), 7.18 (s, 3H), 7.06 (d, j=2.1Hz, 2H), 6.82 (m, 2H), 3.76 (d, J=8.0Hz, 6H), 2.99 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.21,153.72,152.98,145.3,130.26,117.22,114.62,114.23,113.12,55.80,39.42. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 17h 22n 3o 3requires316.1661, found316.1658.
Embodiment four
4 are loaded successively in a Schlenk test tube, 4 '-dichloro nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, two (4-chloro-phenyl-) N of 2-, N-dimethylamino urea, yield is 62%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.40 (d, j=8.8Hz, 2H), 7.32 (d, j=8.8Hz, 2H), 7.26 (s, 1H), 7.16 (d, j=8.8Hz, 2H), 6.99 (d, j=8.8Hz, 2H), 3.03 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.80,147.00,144.39,129.56,129.25,129.17,125.75,121.68,114.75,37.44. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16cl 2n 3orequires324.0670, found324.0661.
Embodiment five
4 are loaded successively in a Schlenk test tube, 4 '-dibromo nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, two (4-the bromophenyl)-N of 2-, N-dimethylamino urea, yield is 63%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.41 (d, j=8.6Hz, 2H), 7.33 (d, j=8.6Hz, 2H), 6.97 (s, 2H), 6.94 (s, 1H), 6.80 (d, j=8.6Hz, 2H), 2.90 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.69,147.49,144.90,132.23,132.12,121.97,117.21,115.23,113.09,37.48. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16br 2n 3orequires411.9660, found411.9653.
Embodiment six
4 are loaded successively in a Schlenk test tube, 4 '-two trifluoromethoxy nitrogen benzide (0.5mmol), sodium iodide (0.1mmol), and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 140 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, two (4-the trifluoromethyl)-N of 2-, N-dimethylamino urea, yield is 43%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.18 (d, j=9.0Hz, 2H), 7.12 (s, 3H), 7.10 (d, j=2.1Hz, 2H), 6.92 (m, 2H), 2.92 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.89,147.20,145.59,145.57,144.59,143.28,143.36,122.48,122.05,121.87,121.74,121.57,119.33,119.19,114.26,37.49. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16f 3n 3o 3requires424.1096, found424.1092.
Embodiment seven
4 are loaded successively in a Schlenk test tube, 4 '-(diazene-1, 2-is disubstituted) dibenzoic acid diethyl ester (0.5mmol), sodium iodide (0.1mmol), and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 36 hours, reaction terminates rear distillation except desolventizing, can 4 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, 4 '-(1-dimethyl carbamoyl hydrazine) dibenzoic acid diethyl ester, yield is 42%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.95 (dd, j=17.7,8.3Hz, 4H), 7.34 (s, 1H), 7.08 (d, j=8.4Hz, 2H), 6.88 (d, j=8.3Hz, 2H), 4.32 (dd, j=11.4,7.1Hz, 4H), 2.94 (s, 6H), 1.35 (q, j=7.2Hz, 6H). 13cNMR (101MHz, CDCl 3) δ 166.39,165.98,159.19,152.08,149.24,131.51,131.00,125.97,123.02,118.79,112.39,60.95,60.54,37.60,14.40,14.35. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 21h 26n 3o 5requires400.1872, found400.1870.
Embodiment eight
3 are loaded successively in a Schlenk test tube, 3 '-dichloro nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, two (3-the chloro-phenyl-)-N of 2-, N-dimethylamino urea, yield is 63%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.26 (dd, j=13.4,5.4Hz, 1H), 7.18 (d, j=8.0Hz, 1H), 7.12 (m, 3H), 6.96 (m, 1H), 6.94 (t, j=1.9Hz, 1H), 6.90 (m, 1H), 6.80 (dd, j=8.1,1.4Hz, 1H), 2.95 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.54,149.71,147.04,135.17,135.01,130.45,130.24,124.49,121.24,120.52,118.08,113.54,111.87,37.54. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16cl 2n 3orequires324.0670, found324.0681.
Embodiment nine
3 are loaded successively in a Schlenk test tube, 3 '-dibromo nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, two (3-the bromophenyl)-N of 2-, N-dimethylamino urea, yield is 63%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.28 (d, j=2.0Hz, 0H), 7.24 (m, 1H), 7.17 (dd, j=13.3,5.1Hz, 2H), 7.10 (m, 2H), 7.00 (m, 2H), 6.83 (m, 1H), 2.93 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.48,149.83,147.10,130.76,130.53,127.38,124.09,123.37,123.32,122.96,118.51,116.40,112.27,37.57. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16br 2n 3orequires411.9660, found411.9664.
Embodiment ten
4-bromine nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N is loaded successively in a Schlenk test tube, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, 1-(4-bromophenyl)-N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-dimethylamino urea, yield is 48%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.44 (m, 1H), 7.35 (m, 2H), 7.28 (m, 1H), 7.13 (m, 2H), 7.02 (m, 1H), 6.95 (m, 2H), 6.88 (m, 1H), 2.93 (d, j=6.3Hz, 6H). 13cNMR (101MHz, CDCl 3) δ 160.23,159.91,148.41,148.01,145.99,145.30,132.20,132.12,129.39,124.68,121.95,121.29,120.77,116.92,115.38,113.58,112.93,37.55,37.51. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 17brN 3orequires334.0555, found334.0555.
Embodiment 11
4-iodine nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N is loaded successively in a Schlenk test tube, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, 1-(4-iodophenyl)-N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-dimethylamino urea, yield is 53%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.56 (m, 2H), 7.32 (t, j=7.9Hz, 2H), 7.25 (m, 1H), 7.10 (m, 2H), 6.90 (m, 7.8Hz, 2H), 6.74 (d, j=8.8Hz, 1H), 2.90 (d, j=7.7Hz, 6H). 13cNMR (101MHz, CDCl 3) δ 160.22,159.84,148.71,148.40,145.97,138.02,129.39,124.69,122.19,121.31,120.75,115.86,113.59,82.67,37.54,37.50. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 17iN 3orequires382.0416, found382.0415.
Embodiment 12
1-(4-bromophenyl)-2-(4-iodophenyl) diazene (0.5mmol) is loaded successively in a Schlenk test tube, sodium iodide (0.1mmol), and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, 2-(4-bromophenyl)-1-(4-iodophenyl)-N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-dimethylamino urea, yield is 43%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.61 (m, 1H), 7.52 (d, j=8.7Hz, 1H), 7.42 (m, 1H), 7.34 (d, j=8.7Hz, 1H), 6.95 (m, 2H), 6.83 (m, 2H), 6.70 (d, j=8.7Hz, 1H), 2.90 (d, j=1.1Hz, 6H). 13cNMR (101MHz, CDCl 3) δ 159.74,159.67,148.30,147.58,145.73,144.99,138.26,138.09,132.21,132.19,128.41,122.27,122.03,117.30,115.80,115.34,113.22,87.83 82.95,37.54. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16brIN 3orequires459.9521, found495.9540.
Embodiment 13
2 are loaded successively in a Schlenk test tube, 2 '-dichloro nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, two (2-chloro-phenyl-) N of 2-, N-dimethylamino urea, yield is 54%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.48 (m, 1H), 7.33 (m, 1H), 7.28 (m, 1H), 7.22 (m, 3H), 7.08 (s, 1H), 6.96 (m, 1H), 6.83 (m, 1H), 3.08 (s, 6H). 13cNMR (101MHz, CDCl 3) δ 159.46,147.62,136.24,131.53,131.08,130.96,130.84,128,20,127.04,125.88,125.82,116.53,113.64,39.80. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 15h 16cl 2n 3orequires324.0670, found324.0674.
Embodiment 14
Nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and methane amide (2ml) is loaded successively in a Schlenk test tube, di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, can 1 be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, 2-diphenyl amino urea, yield is 48%.Its nuclear magnetic data is: 1hNMR (400MHz, DMSO) δ 8.73 (s, 1H), 7.52 (d, j=7.9Hz, 2H), 7.23 (t, j=7.8Hz, 2H), 7.14 (t, j=7.8Hz, 2H), 6.99 (t, j=7.1Hz, 1H), 6.72 (d, j=7.5Hz, 3H), 6.59 (s, 2H). 13cNMR (101MHz, DMSO) δ 163.01,151.82,147.07,134.13,133.13,128.61,127.43,124.40,117.71. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 13h 14n 3orequires228.1137, found228.1145.
Embodiment 15
Nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N-METHYLFORMAMIDE (2ml) is loaded successively in a Schlenk test tube, di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, N-methyl isophthalic acid can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, 2-diphenyl amino urea, yield is 81%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.47 (d, j=7.7Hz, 2H), 7.23 (dd, j=16.0,8.3Hz, 4H), 7.06 (t, j=7.4Hz, 1H), 6.89 (t, j=7.4Hz, 1H), 6.83 (d, j=7.7Hz, 2H), 6.53 (d, j=7.4Hz, 1H), 6.26 (s, 1H), 2.83 (d, j=4.8Hz, 3H). 13cNMR (101MHz, CDCl 3) δ 157.72,145.70,141.49,129.41,128.60,124.61,122.19,121.29,113.35,26.94. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 14h 16n 3orequires242.1293, found242.1288.
Embodiment 16
Nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N-METHYLFORMAMIDE (2ml) is loaded successively in a Schlenk test tube, di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-diethyl-1,2-diphenyl amino urea, yield is 37%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.24 (t, j=7.8Hz, 2H), 7.18 (t, j=7.8Hz, 2H), 7.10 (d, j=7.9Hz, 2H), 7.04 (t, j=7.3Hz, 1H), 6.90 (d, j=8.1Hz, 1H), 6.87 (s, 1H), 6.83 (t, j=7.3Hz, 1H), 3.27 (d, j=6.6Hz, 4H), 1.00 (t, j=7.1Hz, 6H). 13cNMR (101MHz, CDCl 3) δ 160.15,148.86,147.02,129.25,129.23,124.63,121.09,120.96,113.86,41.61,13.00. mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 17h 22n 3orequires284.1763, found284.1759.
Embodiment 17
Nitrogen benzide (0.5mmol), sodium iodide (0.1mmol) and N-N-formyl morpholine N-(2ml) is loaded successively in a Schlenk test tube, di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N '-phenylbenzene morphine-4-carbohydrazide, yield is 39%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.34 (t, j=7.9Hz, 2H), 7.27 (m, 2H), 7.19 (d, j=7.8Hz, 2H), 7.14 (t, j=7.3Hz, 1H), 6.94 (d, j=8.0Hz, 3H), 6.92 (s, 1H), 3.60 (m, 4H), 3.44 (m, 4H). 13cNMR (101MHz, CDCl 3) δ 159.33,148.67,145.94,129.40,129.37,124.80,121.20,120.89,113.38,66.40,45.77.MSESI (m/z): [M+H] +calcdforC 17h 20n 3o 2requires298.1556, found298.1553.
Embodiment 18
Benzylidene aniline (0.5mmol), sodium iodide (0.1mmol) and N is loaded successively in a Schlenk test tube, dinethylformamide (2ml), di-t-butyl peroxide (2mmol) and Benzoyl chloride (0.2mmol) is added with microsyringe, oil bath at 120 DEG C after system being sealed is heated about 24 hours, reaction terminates rear distillation except desolventizing, N can be obtained by simple column chromatography (eluent uses sherwood oil (60 DEG C)) after concentrated, N-dimethyl-2-phenyl-2-anilino ethanamide, yield is 20%.Its nuclear magnetic data is: 1hNMR (400MHz, CDCl 3) δ 7.45 (d, j=7.3Hz, 2H), 7.33 (t, j=7.4Hz, 2H), 7.28 (s, 1H), 7.26 (d, j=3.9Hz, 1H), 7.11 (t, j=7.9Hz, 2H), 6.66 (m, 3H), 5.27 (s, 1H), 3.03 (s, 3H), 2.97 (s, 3H). 13cNMR (101MHz, CDCl 3) δ 170.85,146.23,138.14,129.19,128.91,128.05,127.89,117.87,113.73,58.18,37.03,36.29.Mass-spectrometric data is: MSESI (m/z): [M+H] +calcdforC 16h 19n 2orequires255.1497, found255.1495.

Claims (7)

1. prepare the method for substituted-amino carbamide compound for one kind, it is characterized in that, comprise the following steps: with azobenzene compound and Carbox amide for reactant, with iodide, acyl chlorides and oxygenant for catalyst system, prepare product substituted-amino carbamide compound through hydroacylation reaction;
Wherein, described azobenzene compound is nitrogen benzide, 4,4 '-dimethyl nitrogen benzide, 4,4 '-dimethoxy nitrogen benzide, 4,4 '-dichloro nitrogen benzide, 4,4 '-dibromo nitrogen benzide, 4,4 '-two trifluoromethoxy nitrogen benzide, 3,3 '-dichloro nitrogen benzide, 3,3 '-dichloro nitrogen benzide, 2, the one in 2 '-dichloro nitrogen benzide, 4-iodine nitrogen benzide, 4-chlorine nitrogen benzide, 4-bromine nitrogen benzide, 1-(4-bromophenyl)-2-(4-iodophenyl) diazene;
Described Carbox amide is DMF, N, N-diethylformamide, N, N-dibutyl formamide, N-N-formyl morpholine N-, methane amide or N-METHYLFORMAMIDE;
Described iodide are selected from potassiumiodide, sodium iodide, tetrabutylammonium iodide, ammonium iodide wherein one or more mixture;
Described oxygenant is tertbutyl peroxide, di-t-butyl peroxide or dicumyl peroxide;
Described acyl chlorides is Benzoyl chloride, phenyllacetyl chloride, Bian chlorine, nitrogen nitrogen dimethyl methyl acyl chlorides, Acetyl Chloride 98Min., chloroacetyl chloride a kind of or its more than one mixture;
In described catalyst system, the mass ratio of iodide and oxygenant is 1: 10 ~ 40;
Described substituted-amino carbamide compound is N, N-dimethyl-1,2-diphenyl amino urea, N, N-dimethyl-1,2-di-p-tolyl Urea,amino-, 1,2-bis-(4-p-methoxy-phenyl)-N, N-dimethylamino urea, two (4-chloro-phenyl-) N, the N-dimethylamino urea of 1,2-, two (4-bromophenyl)-N, the N-dimethylamino urea of 1,2-, two (4-trifluoromethyl)-N, the N-dimethylamino urea of 1,2-, 4,4 '-(1-dimethyl carbamoyl hydrazine) dibenzoic acid diethyl ester, two (3-chloro-phenyl-)-N, the N-dimethylamino urea of 1,2-, two (3-bromophenyl)-N, the N-dimethylamino urea of 1,2-, 1-(4-bromophenyl)-N, N-dimethylamino urea, 1-(4-iodophenyl)-N, N-dimethylamino urea, 2-(4-bromophenyl)-1-(4-iodophenyl)-N, N-dimethylamino urea, two (2-chloro-phenyl-) N, the N-dimethylamino urea of 1,2-, 1,2-diphenyl amino urea, N-methyl isophthalic acid, 2-diphenyl amino urea, N, N-diethyl-1,2-diphenyl amino urea, N, N '-phenylbenzene morphine-4-carbohydrazide, N, N-dimethyl-2-phenyl-2-anilino ethanamide.
2. prepare the method for substituted-amino carbamide compound according to claim 1, it is characterized in that: in described catalyst system, the mass percent of iodide is 2% ~ 8%.
3. prepare the method for substituted-amino carbamide compound according to claim 1, it is characterized in that: the mol ratio of described azobenzene compound and iodide is 1: 0.1 ~ 0.2; The mol ratio of azobenzene compound and oxygenant is 1: 2 ~ 4; The mol ratio of azobenzene compound and Carbox amide is 1: 45 ~ 55.
4. prepare the method for substituted-amino carbamide compound according to claim 1, it is characterized in that: described hydroacylation temperature of reaction is 120 ~ 140 DEG C; Reaction times is 24 ~ 36 hours.
5. prepare the method for substituted-amino carbamide compound according to claim 4, it is characterized in that: described hydroacylation temperature of reaction is 120 DEG C; Reaction times is 24 hours.
6. prepare the method for substituted-amino carbamide compound according to claim 1, it is characterized in that: purify after reaction terminates, be specially and first distill, then by concentrated solution by simple column chromatography, substituted-amino carbamide compound can be obtained.
7. prepare the method for substituted-amino carbamide compound according to claim 1, it is characterized in that: reaction is carried out in atmosphere.
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